Transected peripheral nerve injuries from traumatic accidents are known to cause long-term physical disability and neuropathic pain at the injury site. The gold standard of peripheral nerve repair remains the nerve autograft however drawbacks involving multiple surgery sites, lack of donor tissue availability and resulting co-morbidities have reduced its frequent use in the clinical setting. As an alternative to the nerve autograft, a number of polymeric-constructed implants for nerve repair have been introduced onto the market that have shown efficacy in the regeneration of short-gap nerve injuries. Such implants are sutured to either end of the nerve stumps to serve as a bridging device across the gap defect.
While peripheral nerves possess the inherent ability to regenerate and sprout new axons, this innate capacity is often insufficient for the regrowth of an adequately healthy and functional nerve (Soller et al., 20121 Cobianchi et al., 2013). Studies have shown the importance of neurotrophic factors in enhancing the regeneration potential of injured peripheral nerves particularly in gap defects of 10 mm and larger. Thus, research regarding the design of implants for nerve repair has incorporated various single and multiple neurotrophic factors, either in solution or part of a controlled-release mechanism, for enhancing peripheral nerve regeneration. The daily dose of neurotrophic factor delivered to the injury site of the peripheral nerve is critical in the outcome levels of tissue regeneration and functional recovery achieved (Kemp et al., 2011). Under-dosing would have no prominent effect on peripheral nerve regeneration whereas an overdose may hinder the regenerative potential via down-regulation of the necessary receptors (Conti et al., 2004; Goodman and Gilman, 2008). Therefore, tailoring the release kinetics of neurotrophic factors to achieve optimum levels of nerve regeneration is vital for obtaining improvements in functional recovery.
Furthermore, materials comprising the implant should possess intrinsic aspects of native nerve tissue yet be able to maintain adequate mechanical stability and provide the release of sufficient bioactives (APIs) in a sustained manner for the duration of peripheral nerve regeneration. Further research is required to evaluate the role of delivery systems, release mechanisms and release kinetics on the optimal delivery of neurotrophic factors (NTFs) in the most beneficial doses for enhanced axonal sprouting. Such factors must be tailored to deliver NTF doses that correspond to the regeneration rate of the injured tissues. Furthermore, understanding the mechanisms behind the phenomenon of initial burst release and factors controlling the characteristics of sustained release profiles will allow researchers to gain a deeper insight and knowledge on modification techniques to regulate the delivery of incorporated bioactives.
Known biodegradable implants typically comprise a carrier matrix (also called a scaffold) that is impregnated with active pharmaceutical ingredient (API). Once implanted into an animal or human body, the implant comes into contact with bodily fluid causing swelling whilst concomitantly allowing the API to migrate via dissolution processes out of the carrier matrix (scaffold) to a target site to treat a disease, condition and/or injury. Often the swelling of the carrier matrix (scaffold) places unwanted pressure on surrounding tissue and/or slows API release to the target site. Swelling may even result in displacement of the implant preventing the API from reaching its target site.
Accordingly, there is a need for biodegradable implants that at least ameliorate one of the disadvantages known in the prior art and/or described above.